On 8 May 2018, Janssen announced that daratumumab has been granted approval by the US Food and Drug Administration (FDA) for the treatment of newly diagnosed multiple myeloma (NDMM) patients. The approval is specifically for use in combination with bortezomib, melphalan, and prednisone (VMP), following data from the phase III ALCYONE clinical trial, which showed a 50% reduction in the risk of disease progression with the addition of daratumumab. Details of the full study were published in the New England Journal of Medicine earlier this year by Maria Victoria Mateos and colleagues.
Daratumumab was initially tested in the relapsed setting in both the POLLUX (daratumumab, lenalidomide, and dexamethasone, [DRd]) and CASTOR (daratumumab, bortezomib, and dexamethasone, [DVd]) clinical trials and proved highly effective. In general, a move to using daratumumab in the frontline setting is widely supported as a response to the first regimen is usually the best, leading to the longest period of remission. Therefore, physicians treating MM are advised to give the most effective therapy at the outset, so it is welcome news that daratumumab can now feature at this early stage in the US. However, whether this particular combination is the most effective is subject to debate.
Jesus Berdeja spoke on Onc Live saying, "News today that daratumumab has been approved in the frontline treatment of myeloma...We were all waiting for this to happen, it's almost like a no-brainer. We knew that this was an easy drug to combine and I really think it's going to augment our treatment...getting much deeper remissions and hopefully getting patients to the MRD [minimal residual disease] negative states that we know have become the new gold standard in terms of therapy for myeloma." However, Vincent Rajkumar took to Twitter to give his opinion: "Daratumumab approval for untreated myeloma: - Trial design was biased, endpoint not correct. Cannot be used to recommend routine Dara use in frontline setting - FDA shouldn’t have approved. Sets bad precedent. - No one uses VMP. In effect will be combined with VRD/KRD." Dr Rajkumar concedes that this approval may help some patients with high-risk MM, but argues that with the current system in the US, "which rewards administration of more expensive chemo with more take-home dollars", this may lead to patients being offered quadruplet therapy instead of transplants, adding further to the growing cost of treatment.
This opinion was shared by others, who agreed that a more effective combination, in reality, will be the use of daratumumab in a quadruplet as either D-VRd or D-KRd. However, Maria Mateos defended the study arguing, "The endpoint is the same used in all trials supporting approvals". She also explained that D-VMP is an affordable regimen in many countries where VRd and KRd will be too expensive.